Novel approaches to control biofilm infections.

Biofilms are matrix-enclosed microbial aggregations that adhere to biological or non-biological surfaces. They represent a significant and incompletely understood mode of growth for bacteria and fungi. Biofilm infections cause many deaths and high health costs worldwide. Biofilm infections on indwelling devices or implants are difficult to eradicate because of their much better protection against macrophages and antibiotics, compared to free living cells, leading to severe clinical complications often with lethal outcome. One promising approach to combat biofilm infections independent from the conventional control by antibiotics is the generation of functional surfaces preventing the attachment of bacteria. Another aim is the communication machinery used by bacteria to establish a biofilm, the so called quorum-sensing. Here, small diffusible compounds are produced and sensed by the producing cells to measure their concentration and hence cell density. Natural compounds and synthetic analogues have been used successfully to prevent biofilm formation by quorum-quenching. These compounds are still in the preclinical phase, often struggling with toxicity. A principal problem of quorum-quenchers is their high species specificity, resulting in the control of only some pathogenic strains leaving other pathogens untouched. A field still in its infancy is the control of virulence factors expression not preventing the biofilm but suppressing its virulence. This review will give an overview over the pros and cons of the individual targets and an outlook of future developments.